Is DDA1 p.Ser23Pro (c.67T>C) pathogenic?

DDA1 p.Ser23Pro (c.67T>C) is classified Uncertain significance in DDA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.6303); Absent from gnomAD v4.1.

How common is DDA1 p.Ser23Pro (c.67T>C) in the general population?

DDA1 p.Ser23Pro (c.67T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDA1 p.Ser23Pro (c.67T>C)?

AlphaMissense predicts likely pathogenic (score 0.6303) — an in-silico prediction, not a clinical call.

DDA1 p.Ser23Pro

c.67T>C · VCV4238330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6303 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6303	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.66, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 6,332 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDA1
Protein: p.Ser23Pro
Coding: c.67T>C
MANE Select: NM_024050
Type: single nucleotide variant
Location: chr19:17314086 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 67.25 · 30 PDB

Full DDA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDA1 p.Ala21Val Uncertain significance ★ ⚠ same type
DDA1 p.Ala91Val Uncertain significance ★ ⚠ same type
DDA1 p.Arg31Gln Uncertain significance ★ ⚠ same type
DDA1 p.Arg31Trp Uncertain significance ★ ⚠ same type
DDA1 p.Asn67Tyr Uncertain significance ★ ⚠ same type
DDA1 p.Asp101Tyr Uncertain significance ★ same type
DDA1 p.Asp22Asn Uncertain significance ★ ⚠ same type
DDA1 p.Glu100Lys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dda1-p-ser23pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown